We have developed an algorithm for structure-based prediction of the pH dependence of the transition temperature (Tm) of proteins. The DG determined at one pH value by DSC is used as a reference point. The pH-dependent component of the free energy of stabilization of the native state is calculated from structure and used to "correct" the calorimetric DG in order to account for the effects of pH on the stability of the protein. In order to test the algorithm we have collected Tm vs pH for horse heart cytochrome-c over a range of condition of ionic strength.